Abstract
PURPOSE: Although many studies have indicated that atopic dermatitis (AD) could contribute to the risk of keratoconus (KC), the causality between AD and KC remains controversial. This study aimed to explore the potential causal associations between AD and KC. METHODS: Instrumental variables for both exposures and outcomes were obtained from large-scale genome-wide association study summary statistics from previous meta-analyses. Mendelian randomization (MR) was applied to infer causal associations between AD and KC. Our main analyses were conducted by inverse-variance weighted (IVW) method multiplicative random effect model, complemented with additional five models and sensitivity analyses. Reverse MR analysis was applied to determine the direction of the causal association between AD and KC. RESULTS: Both IVW and weighted median methods revealed a causal effect of AD on KC (IVW odds ratio [OR], 1.475; P = 4.16 × 10-4; weighted median OR, 1.351; P = 7.65 × 10-3). The weighted mode, simple mode, and MR Egger methods demonstrated consistent direction of causality. Evidence from all sensitivity analyses further supported these associations. Reverse MR analyses did not suggest causal effects of KC on AD. CONCLUSIONS: This study supported a significant causal effect of AD on KC, and reverse MR analysis proved that the causal association was unilateral. TRANSLATIONAL RELEVANCE: This study provides valid evidence that regular ophthalmic examinations are recommended for patients with AD to detect and prevent KC at an early stage.